Structure-based drug design against pandemic influenza using all-atom molecular dynamics and docking

COMP 264

Rashi Goyal,, Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794 and Robert C. Rizzo,, Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-3600.
Avian influenza strain H5N1 has been identified as a serious pandemic threat due to its extremely high mortality rate and risk of developing into a human pathogenic strain. Although H5N1 is sensitive to currently approved drugs oseltamivir and zanamivir, which target the viral enzyme neuraminidase (NA), point mutations H274Y and N294S in NA have been identified in some strains which confer drug resistance. In this study, we are using crystallographic structures as a starting point for simulations of NA tetramers, bound with known inhibitors, with the goal of elucidating the origins of drug resistance due to mutation. In parallel, we are developing and applying virtual screening protocols using the program DOCK, for targeting NA using the IBM BlueGene platform, with the goal of discovering novel drug leads. Results from these studies which include free energy calculations and analyses, as well as DOCK benchmarking, cross-docking, and enrichment for virtual screening, will be presented.

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009